NEW YORK (Reuters Health) - Ceftazidime in combination with
avibactam is effective for treating ceftazidime-resistant
urinary tract and intra-abdominal infections, according to
results from the REPRISE study.

The prevalence of multidrug-resistant Gram-negative
pathogens is increasing worldwide. Avibactam has a broader
spectrum of activity than other available beta-lactamase
inhibitors.

Dr. Yehuda Carmeli from Tel Aviv Sourasky Medical Center,
Israel, and colleagues investigated the efficacy, safety, and
tolerability of ceftazidime-avibactam versus best available
therapy in a phase 3 study of 333 patients with complicated
urinary tract infection or complicated intra-abdominal infection
due to ceftazidime-resistant Gram-negative pathogens.

Most (97%) of the 168 patients in the best available
therapy group were treated with carbapenem monotherapy,
according to the April 20 Lancet Infectious Diseases online
report.

Most patients in both groups were infected with
Enterobacteriaceae (most commonly Escherichia coli and
Klebsiella pneumoniae).

In the combined group, the overall proportions of patients
with a clinical cure were 91% with ceftazidime-avibactam and 90%
with best available therapy.

Results were similar in the subgroups. For patients with
complicated urinary tract infections, the clinical cure rates
were 92% with ceftazidime-avibactam versus 94% with best
available therapy. For patients with complicated intra-abdominal
infections, the clinical cure rates were 80% with
ceftazidime-avibactam and 55% with best available therapy.

Microbiological response rates in the urinary tract
infection group were higher with ceftazidime-avibactam (82%)
than with best available therapy (64%).

Adverse event rates were similar with ceftazidime-avibactam
(31%) and best available therapy (39%), with most events
classified as mild or moderate in intensity.

"These promising results support the use of
ceftazidime-avibactam as a potential alternative to carbapenems
in patients with resistant Gram-negative infections," the
researchers concluded.

Dr. Florian M.E. Wagenlehner from Justus-Liebig University,
Giessen, Germany, who coauthored an accompanying editorial, told
Reuters Health by email, "The main message is that
ceftazidime-avibactam is noninferior to carbapenems (or best
available therapy) in patients with complicated abdominal or
urinary infections, although in this study mainly (>90%) urinary
infections were studied."

"On the one hand, it has some increased efficacy over
carbapenems in bacteria with Klebsiella pneumoniae
carbapenemases," he said. "On the other hand, it would well
serve as a carbapenem saving strategy to save these last-resort
antibiotics."

Dr. Carmeli did not respond to a request for comments.

AstraZeneca funded the trial, provided grants to Dr.
Carmeli, and employed the rest of the authors.